We propose a study, iMAN: integrated Molecular & Affiliation Network Analysis of HIV Transmission, which integrates molecular phylogenetic analysis with systems science methodologies to advance our understanding of the venue-based affiliation networks whereby the human immunodeficiency virus (HIV) is transmitted. iMAN will examine the highest HIV-risk group, young Black men who have sex with men (YBMSM) aged 16 to 29 in Houston, TX, and Chicago, IL, based on the cohorts of an ongoing multi-site longitudinal affiliation network project (YMAP: Young Men's Affiliation Project). iMAN aims to further advance the utility of affiliation network analysis by introducing a novel way of addressin fundamental questions about human health behavior, grounded in biological validation, to alleviate racial/ethnic health disparities in HIV-infection rates in regard to YBMSM. YBMSM socialize in a variety of contexts, both real and virtual, and these venues can involve network relationships that increase the risk of HIV/sexually-transmitted infections (STI) acquisition. Affiliation network analysis can serve as a methodological tool to investigate associations between individuals' affiliations with risky social venues and HIV risk or prevention. Affiliation network analysis alone, however, has limitations in providing grounded results. Thus, we propose to validate our findings using biological markers in the HIV virus itself. iMAN will apply phylogenetic techniques to the affiliation network analysis to simultaneously analyze social relations (epidemiology information) and molecular viral relatedness (molecular information) in a multi-level approach. iMAN proposes to use phylogenetic analysis to help characterize the clustering patterns of HIV infection within YBMSM from different patterns of venue affiliation. The objective of iMAN is to characterize the epidemiology of HIV transmission by identifying venue-based clustering of HIV-infected YBMSM across different cities using state-of-the-art molecular epidemiology methods. The resulting venue- based and genetic transmission clusters will be further examined to describe the transmission patterns of the epidemic in Houston and Chicago as well as to compare and contrast the patterns between the two cities. Our specific aims are to (1) identify HIV-transmission clusters and describe the patterns of epidemic spread by identifying (a) genetic clusters between HIV-infected YBMSM using phylogenetic analysis, and (b) venue- based social clusters using affiliation network analysis; (2) compare genetic clusters and venue-based social clusters to determine venue-based HIV risk at the local level. The findings from this research are expected to provide new directions for developing venue-based network interventions informed by molecular science and to have an impact on network interventions that target those most at risk of HIV/STI infection.